ArticleThe Journal of biological chemistry
Glycosylation limits forward trafficking of the tetraspan membrane protein PMP22.
Article in The Journal of biological chemistry. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 25 citations in OpenAlex.
- Protein-enhanced small molecule disruptors of ordered membrane domains.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Peripheral Myelin Protein-22 and Its Prominence in Charcot-Marie-Tooth Disease.Chemical reviews · 2026Review
- Longitudinal analysis of lipid changes in the sciatic nerve caused by overexpression of PMP22 in murine models of CMT1A.Journal of lipid research · 2026Article
- Pharmacological tools to modulate ordered membrane domains and order-dependent protein function.Communications chemistry · 2026Article
- Characterising PMP22-Proximal Partners in a Schwann Cell Model of Charcot-Marie-Tooth Disease Type1A.Biology · 2025Article
- Pharmacological Tools to Modulate Ordered Membrane Domains and Order-Dependent Protein Function.bioRxiv : the preprint server for biology · 2025Article
- RER1 regulates lipid metabolism in monocytes and macrophages.Cellular and molecular life sciences : CMLS · 2025Article
- Dimerization is required for the glycosylation of S1-S2 linker of sea urchin voltage-gated proton channel Hv1.Biophysical journal · 2024Article
- Small-Molecule Modulators of Lipid Raft Stability and Protein-Raft Partitioning.bioRxiv : the preprint server for biology · 2024Article
- Disrupting the transmembrane domain interface between PMP22 and MPZ causes peripheral neuropathy.iScience · 2024Article
- Time-resolved interactome profiling deconvolutes secretory protein quality control dynamics.Molecular systems biology · 2024Article
- Roles for PMP22 in Schwann cell cholesterol homeostasis in health and disease.Biochemical Society transactions · 2024Review
- The proteostasis interactomes of trafficking-deficient variants of the voltage-gated potassium channel KThe Journal of biological chemistry · 2024Article
- Dark nanodiscs for evaluating membrane protein thermostability by differential scanning fluorimetry.Biophysical journal · 2024Article
- AAV-mediated editing of PMP22 rescues Charcot-Marie-Tooth disease type 1A features in patient-derived iPS Schwann cells.Communications medicine · 2023Article
- Mechanisms and treatment strategies of demyelinating and dysmyelinating Charcot-Marie-Tooth disease.Neural regeneration research · 2023Review
- A novel mouse model of CMT1B identifies hyperglycosylation as a new pathogenetic mechanism.Human molecular genetics · 2022Article
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7 authors at 2 institutions in 1 country.
Funding
Abstract
Peripheral myelin protein 22 (PMP22) folds and trafficks inefficiently, with only 20% of newly expressed protein trafficking to the cell surface. This behavior is exacerbated in many of the mutants associated with Charcot-Marie-Tooth disease, motivating further study. Here we characterized the role of N-glycosylation in limiting PMP22 trafficking. We first eliminated N-glycosylation using an N41Q mutation, which resulted in an almost 3-fold increase in trafficking efficiency of wildtype (WT) PMP22 and a 10-fold increase for the severely unstable L16P disease mutant in HEK293 cells, with similar results in Schwann cells. Total cellular levels were also much higher for the WT/N41Q mutant, although not for the L16P/N41Q form. Depletion of oligosaccharyltransferase OST-A and OST-B subunits revealed that WT PMP22 is N-glycosylated posttranslationally by OST-B, whereas L16P is cotranslationally glycosylated by OST-A. Quantitative proteomic screens revealed similarities and differences in the interactome for WT, glycosylation-deficient, and unstable mutant forms of PMP22 and also suggested that L16P is sequestered at earlier stages of endoplasmic reticulum quality control. CRISPR knockout studies revealed a role for retention in endoplasmic reticulum sorting receptor 1 (RER1) in limiting the trafficking of all three forms, for UDP-glucose glycoprotein glucosyltransferase 1 (UGGT1) in limiting the trafficking of WT and L16P but not N41Q, and calnexin (CNX) in limiting the trafficking of WT and N41Q but not L16P. This work shows that N-glycosylation is a limiting factor to forward trafficking PMP22 and sheds light on the proteins involved in its quality control.
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